J Korean Neurol Assoc > Volume 20(6); 2002 > Article

Journal of the Korean Neurological Association 2002;20(6): 660-667.

"선택적 Cyclooxygenase-2 억제제인 R o f e c o x I b 가 쥐의 해마에서 만성 저혈류로 유발된 아포프토시스에 미치는 효과"

최영빈 , 정성우 김영인 이광수 김범생 이희진 이원선 박상희

가톨릭대학교 의과대학 신경과학교실,가톨릭대학교부속 성가병원 임상의학연구실

"The Selective Cyclooxygenase-2 Inhibitor Rofecoxib Reduces Chronic Cerebral Hypoperfusion-induced Apoptosis in the Rat Hippocampus"

Young-Bin Choi, M.D

"Department of Neurology, College of Medicine, The Catholic University of Korea Clinical Medical Research Institute, Holy Family Hospital, The Catholic University of Korea"

Abstract

"Background : Chronic cerebral hypoperfusion induced by permanent occlusion of bilateral common carotid arteries (2VO) in rats caused cognitive deficits and neuronal damage. Cyclooxygenase-2 (COX-2) inhibitor was reported to attenuate both post-ischemic prostaglandin accumulation and neuronal damage. We studied the expression of mRNA of COX-2 in the hippocampus during hypoperfusion and the effectiveness of selective cyclooxygenase-2 inhibitor, rofe-coxib, in preventing the neuronal damage of this model. Methods : Bilateral common carotid arteries of the rat were ligated with silk sutures. The expression of mRNA for COX-1 and COX-2 were detected by the RT-PCR. The first group of animals (n=6) was treated with rofecoxib (10 mg/kg, I.p.) 7 days after operation and the following 7 days. The second group of animals (n=6) was treated with diclofenac sodium (9mg/kg, i.p.) and the third group of animals (n=5) was treated with vehicle (DMSO). TdT-mediated dUTP nick end labeling (TUNEL) technique was performed to esti-mate delayed cell death. Results : Bilateral carotid artery occlusion (2VO) was shown to induce apoptotic morphology and DNA strand break in hippocampal neurons from 7 days with a peak at 14, 28 days. mRNA of COX-2 appeared in the frontal cortex (14, 28 days) and hippocampus (14, 28, 63 days). Treatment with rofecoxib significantly (p<0.05) attenuated the number of TUNEL-labeled cells in the hippocampus, whereas the cells of the diclofenac treated group were not protected. Conclusions : We concluded that COX-2 might contribute to cell death of pyramidal cells of the hippocampus of hypoperfusion and selective COX-2 inhibitor, rofecoxib, could prevent the neuronal damage.Key Words : Hypoperfusion, Apoptosis, Cyclooxygenase, Vascular dementia"